37.2.1 Patient History Leading to the Specific Problem

This 52-year-old Middle Eastern woman reported injection of cross-linked hyaluronic acid (HA) filler for correction of infraorbital hollows, with immediate onset of postprocedural swelling. She reported that the filler was injected overseas in a group setting, with several patients in one examination room and the physician moving quickly from injection of one patient to the next. One milliliter of filler was injected to each side. The onset of swelling was within 24 hours of injection. It worsened over the ensuing week. The treating physician advised the patient that the swelling would resolve spontaneously. At the time of consultation, the swelling had persisted for 3 months. The patient reported that it was often more pronounced in the mornings.

37.2.2 Anatomic Description of the Patient’s Current Status

On visual inspection and palpation, the patient presented with bilateral, diffuse, soft, compressible infraorbital swelling. The swelling was more pronounced on the left than the right side. There were no symptoms or signs of inflammation, such as erythema, pain, tenderness, or warmth of the swollen regions. The patient had mild limitation of lower eyelid movement due to the swelling. She reported no paresthesia (Fig. 37-6).

37.2.3 Diagnosis

Inappropriate placement of HA filler.

37.2.4 Recommended Solution to the Problem

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  The acute-onset, persistence, and noninflammatory nature of the swelling were consistent with inappropriate placement of the filler and/or overfilling, causing lymphatic outflow obstruction. The increased swelling in the mornings was also consistent with lymphatic outflow obstruction, since fluid will accumulate after several hours lying down.

  
  
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  Diagnostic ultrasonographic imaging would be optimal prior to intervention, to determine the precise location of the filler and to provide evidence confirming it as HA. The patient declined this investigation.

  
  
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  Hyaluronidase will enzymatically break down unwanted HA filler. It may also be considered for the tissue surrounding non-HA filler deposits, to aid in their dispersion (this is discussed further in case 3 below). The Lambros method entails dilution of the hyaluronidase with lidocaine to decrease discomfort during and after injection, plus epinephrine with the objective of localizing the hyaluronidase, to maximize its efficacy and limit its dispersion to areas where it is not indicated.

  
  
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  After careful analysis of the risks versus the benefits of empiric treatment with hyaluronidase, this was performed as described in the following.

37.2.5 Technique

Ovine hyaluronidase (Vitrase, 200 USP Units/mL, Bausch & Lomb) was diluted 1:4 with 1% lidocaine (10 mg/mL) plus epinephrine (1:100,000) suspension. Using sterile technique, 0.6 mL of this diluted hyaluronidase was injected intralesionally and in the adjacent, surrounding subcutaneous tissue, via serial 0.1-mL boluses with a 32-G needle. Mild tissue pressure and molding were applied after injection, with the aim of dispersing the hyaluronidase throughout the areas of swelling.

37.2.6 Postoperative Photographs and Critical Evaluation of Results

At follow-up, 12 days after hyaluronidase injection, the infraorbital swelling was significantly improved. There was mild residual bilateral swelling. The patient was advised that further hyaluronidase injection could achieve further improvement. The patient was noncompliant with recommended follow-up 2 to 3 weeks later, stating that she wished to return for further treatment after overseas travel (Fig. 37-7).

37.2.7 Teaching Points

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  Acute-onset swelling or nodules may be defined as those that occur within 48 hours of filler implantation. If they are noninflammatory on the basis of history, visual inspection, and palpation, they may be a result of filler misplacement or overfilling. Postinjection displacement of filler may also occur, especially in highly mobile regions or when the filler has been implanted into muscle.

  
  
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  The periocular region is vulnerable to swelling and nodules because of its anatomically unforgiving nature, its thin skin which makes underlying contour abnormalities more visible, and its propensity for lymphatic outflow obstruction.

  
  
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  Different fillers have different propensities to absorb water. Highly hygroscopic HA fillers are not ideally suited to the periorbital area, and especially not to the region of the lower lid–cheek junction. Physiological hydration of an inappropriate product may exacerbate preexisting edema or create it.

  
  
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  A common cause of acute swelling following periocular filler injection is inadvertent, misplaced implantation, resulting in lymphatic outflow obstruction. The aging eyelid may have an increased susceptibility to this, due to deflation and descent of its supporting fat compartments. Anatomical study of the lower eyelid by Shoukath et al, and correlation with postoperative chemosis and edema, has provided insights into the principal points within the lymphatic system at which obstruction is likely to occur. The deep lymphatic system of the eyelid commences at the conjunctiva, pierces the tarsal plate, and descends deep to the orbicularis oculi. This connects through the muscle with a superficial lymphatic system. Lymphatic vessels then travel through the orbicularis retaining ligament, to run within the suborbicularis oculi fat (SOOF), in the roof of the prezygomatic space. At the zygomaticocutaneous ligament, the vessels descend to preperiosteal fat and then follow branches of the facial nerve to lymph nodes within the parotid gland. The superficial lymphatic system drains the eyelid skin, passing superficial to the orbicularis oculi muscle, with connections through the muscle to the deep system. Laterally, it reaches preauricular lymph nodes, while, medially, it parallels the path of the facial vein and drains into mandibular and submandibular lymph nodes. The key regions at which obstruction of the lateral deep lymphatic system is most likely are at the orbicularis retaining ligament and the zygomaticocutaneous ligament.

  
  
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  Preexisting malar or lower lid edema may be considered a contraindication to infraorbital filler injection, since it confers an increased risk for prolonged, postprocedural swelling. The incidence of malar or lower lid edema is relatively high. In a series of 114 randomly selected patients, Goldberg et al found that 32% had some degree of it, and 13% had malar mounds (i.e., triangular areas of fullness inferior and lateral to the orbital rim [Fig. 37-1]).

  
  
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  HA fillers are strongly recommended for the periocular region, since their reversibility with hyaluronidase confers maximal safety and allows misplaced or excessive filler to be removed noninvasively.

  
  
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  Slight undercorrection of the infraorbital region is recommended to avoid aesthetically undesirable convexity, with no more than 0.5 mL of filler implanted per side during each session. An interval of at least 3 to 4 weeks is recommended before further injections are performed.

  
  
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  In general, as in all branches of medicine and surgery, filler problems are best diagnosed definitively and a treatment plan formulated based on this diagnosis. However, it is not uncommon for patients with filler problems to refuse diagnostic investigations. This is primarily due to a desire for prompt treatment with rapid resolution of the problem. It is the responsibility of the treating physician to determine what is in the patient’s best interests, considering the risks versus the benefits of empiric treatment. In situations where the risks outweigh the benefits, patients should be counseled that diagnostic investigations must be undertaken prior to treatment, to assure safe and effective management.

  
  
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  Since intracutaneous and subcutaneous injection of exogenous hyaluronidase has a favorable safety profile, its empiric use is justified when risk–benefit analysis indicates this to be appropriate. Besides the specific preparation of ovine hyaluronidase used for treatment of this patient, other hyaluronidase preparations are available on a geographic basis. Another preparation of ovine hyaluronidase (Hyalase, 1500 IU as a freeze dried powder 1 mL ampule, Sanofi-Aventis Australia Pty Ltd) can be diluted with saline to 50 IU per mL for treatment of aesthetic complications (compared with 150 IU per mL or greater for vascular indications). Recombinant human hyaluronidase (Hylenex, 150 USP units/mL, Halozyme Therapeutics, San Diego, CA) can be diluted in a similar manner to ovine hyaluronidase (Vitrase).

  
  
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  Patients should be advised as part of the informed consent process for hyaluronidase that temporary bruising and swelling are expected after injection. Multiple sessions of hyaluronidase injection are often required, particularly with HA fillers of high longevity. An interval of at least 1 week is recommended between sessions. Infraorbital hollows are likely to reappear after hyaluronidase. Their correction will require injection of filler with appropriate technique.

  
  
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  Patients should also be warned that the extent of improvement with hyaluronidase cannot be predicted and may be incomplete. In the anecdotal experience of one of the authors (H. S.), some patients who experience an episode of swelling after suboptimal periocular filler injection are prone to swelling after the filler is removed and even if filler is reimplanted subsequently with appropriate technique.

  
  
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  Hyaluronidase has also been advocated as a rescue treatment in cases of inadvertent intra-arterial injection of HA filler and consequent filler embolization. In a real-time, fresh, frozen cadaver model, Magnusson and Papadopoulos demonstrated that HA filler implanted into facial arteries can be degraded transarterially by exogenous hyaluronidase injected into the surrounding soft tissue. DeLorenzi has described transarterial degradation of HA filler within closed cadaveric arterial segments immersed in hyaluronidase at therapeutic doses. Zhu et al prospectively evaluated the efficacy of retrobulbar hyaluronidase injection in four patients whose vision loss was due, respectively, to branch retinal artery occlusion, posterior ischemic optic neuropathy (PION), ophthalmic artery occlusion, and both branch retinal artery occlusion and PION. None of the patients achieved substantial retinal artery recanalization or improvement in visual acuity following one or two retrobulbar injections of high-dose (1,500 or 3,000 units) ovine testicular hyaluronidase (Shanghai First Biochemical Pharmaceutical Corporation) at least 4 hours after the onset of vision loss. In support of this finding, the authors recently reported failure of hyaluronidase to pass transarterially in a pilot, real-time, in vivo model, suggesting that permeability of the living arterial wall differs significantly from permeability in the cadaver.